title: Epigenetic events in normal colonic mucosa surrounding colorectal cancer lesions.
abstract: Gene inactivation by promoter hypermethylation has been demonstrated in the colonic mucosa of colorectal cancer (CRC) patients. However, current data do not prove direct involvement of this epigenetic modification in the early stages of CRC. Promoter methylation profiles of E-cadherin, hMLH1, MGMT, p16(INK4a), p15(INK4b) and p14(ARF); mutations of K-ras, B-raf and TP53 and microsatellite instability (MSI) were examined in normal and cancerous colonic mucosal tissue in 82 CRC patients using methylation-specific PCR assays. Methylation of hMLH1 and MGMT in normal mucosa correlated significantly with MSI and K-ras activation in neighbouring cancerous mucosal tissues. Similarly, poorly differentiated tumours were associated with methylated p16(INK4a) and E-cadherin in neighbouring normal colonic tissues (NCTs). Our results indicate that epigenetic changes in mucosa surrounding colorectal neoplastic lesions may describe a 'field cancerisation' phenomenon that may occur previous to genetic alterations in early stages of carcinogenesis.
authors.affiliation: Laboratory of Pharmacogenomics, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. nrhuerto@unav.es
authors.forename: N
authors.initials: N
authors.lastname: Ramírez
authors.forename: E
authors.initials: E
authors.lastname: Bandrés
authors.forename: A
authors.initials: A
authors.lastname: Navarro
authors.forename: A
authors.initials: A
authors.lastname: Pons
authors.forename: S
authors.initials: S
authors.lastname: Jansa
authors.forename: I
authors.initials: I
authors.lastname: Moreno
authors.forename: F
authors.initials: F
authors.lastname: Martínez-Rodenas
authors.forename: R
authors.initials: R
authors.lastname: Zárate
authors.forename: N
authors.initials: N
authors.lastname: Bitarte
authors.forename: M
authors.initials: M
authors.lastname: Monzó
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D048493:Proto-Oncogene Proteins B-raf